Abstract:
:Antiangiogenic therapy is associated with increased radiographic responses in glioblastomas, but tumors invariably recur. Because tumor-associated macrophages have been shown to mediate escape from antiangiogenic therapy in preclinical models, we examined the role of macrophages in patients with recurrent glioblastoma. We compared autopsy brain specimens from 20 patients with recurrent glioblastoma who received antiangiogenic treatment and chemoradiation with 8 patients who received chemotherapy and/or radiotherapy without antiangiogenic therapy or no treatment. Tumor-associated macrophages were morphologically and phenotypically analyzed using flow cytometry and immunohistochemistry for CD68, CD14, CD163, and CD11b expression. Flow cytometry showed an increase in macrophages in the antiangiogenic-treated patients. Immunohistochemical analysis demonstrated an increase in CD68+ macrophages in the tumor bulk (P < .01) and infiltrative areas (P = .02) in antiangiogenic-treated patients. We also observed an increase in CD11b+ cells in the tumor bulk (P < .01) and an increase in CD163+ macrophages in infiltrative tumor (P = .02). Of note, an increased number of CD11b+ cells in bulk and infiltrative tumors (P = .05 and P = .05, respectively) correlated with poor overall survival among patients who first received antiangiogenic therapy at recurrence. In summary, recurrent glioblastomas showed an increased infiltration in myeloid populations in the tumor bulk and in the infiltrative regions after antiangiogenic therapy. Higher numbers of CD11b+ cells correlated with poor survival among these patients. These data suggest that tumor-associated macrophages may participate in escape from antiangiogenic therapy and may represent a potential biomarker of resistance and a potential therapeutic target in recurrent glioblastoma.
journal_name
Neuro Oncoljournal_title
Neuro-oncologyauthors
Lu-Emerson C,Snuderl M,Kirkpatrick ND,Goveia J,Davidson C,Huang Y,Riedemann L,Taylor J,Ivy P,Duda DG,Ancukiewicz M,Plotkin SR,Chi AS,Gerstner ER,Eichler AF,Dietrich J,Stemmer-Rachamimov AO,Batchelor TT,Jain RKdoi
10.1093/neuonc/not082subject
Has Abstractpub_date
2013-08-01 00:00:00pages
1079-87issue
8eissn
1522-8517issn
1523-5866pii
not082journal_volume
15pub_type
杂志文章相关文献
NEURO-ONCOLOGY文献大全abstract:BACKGROUND:Promoter methylation of O(6)-methylguanine-DNA methyltransferase (MGMT) is an important predictive biomarker in glioblastoma. The T variant of the MGMT promoter-enhancer single nucleotide polymorphism (SNP; rs16906252) has been associated with the presence of MGMT promoter methylation in other cancers. We ex...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/nov064
更新日期:2015-12-01 00:00:00
abstract::The purpose of this study was to determine the dose-limiting toxicities, maximum tolerated dose, pharmacokinetics, and intratumor and brain distribution of motexafin gadolinium (MGd) with involved field radiation therapy in children with newly diagnosed intrinsic pontine gliomas. MGd was administered as a 5-min intrav...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1215/15228517-2008-043
更新日期:2008-10-01 00:00:00
abstract::Survivorship has become a significant topic within oncologic care. The tools and means by which the provision of survivorship care can be implemented and delivered are in development and are the focus of significant research oncology-wide. These tools and methods include innovations of survivorship care delivery, surv...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/noy110
更新日期:2018-11-09 00:00:00
abstract::Recurrence of primary central nervous system lymphoma (PCNSL) after initial diagnosis and treatment occurs within 2 years in most patients, and relapse after 5 years is rare. We evaluated late relapse in our PCNSL population. We identified 10 patients from our database of 378 patients (268 achieved a complete response...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/nor014
更新日期:2011-05-01 00:00:00
abstract:BACKGROUND:Whole-brain radiotherapy (WBRT) in patients with brain metastases (BM) is associated with neurocognitive decline. Given its crucial role in learning and memory, efforts to mitigate this toxicity have mostly focused on sparing radiation to the hippocampus. We hypothesized that BM are not evenly distributed ac...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/noz023
更新日期:2019-05-06 00:00:00
abstract::Background Notch signaling is deregulated in human gliomas and may play a role in their malignancy. However, the role of each Notch receptor in glioma cell differentiation and progression is not clear. We examined the expression pattern of Notch receptors and compared it with differentiation markers in glioma cell lin...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/not168
更新日期:2014-01-01 00:00:00
abstract::With the median survival of 14.6 months following best available standard of care, malignant gliomas (MGs) remain one of the biggest therapeutic challenges of the modern time. Although the last several decades have witnessed tremendous advancement in our understanding of MG and evolution of many successful preclinical...
journal_title:Neuro-oncology
pub_type: 杂志文章,评审
doi:10.1093/neuonc/now109
更新日期:2017-03-01 00:00:00
abstract::Diffuse intrinsic pontine glioma (DIPG) has proven to be one of the most challenging of all pediatric cancers. Owing to a historical reticence to obtain tumor tissue for study, and based on an erroneous assumption that the biology of DIPG would mirror that of supratentorial high-grade astrocytomas, innumerable studies...
journal_title:Neuro-oncology
pub_type: 杂志文章,评审
doi:10.1093/neuonc/nox021
更新日期:2017-08-01 00:00:00
abstract::Glioblastoma (GBM) is the most common malignant primary brain tumor. Its incidence continues to increase in the elderly because the older segment of the population is growing faster than any other age group. Most clinical studies exclude elderly patients, and "standards of care" do not exist for GBM patients aged >70 ...
journal_title:Neuro-oncology
pub_type: 杂志文章,评审
doi:10.1093/neuonc/nou063
更新日期:2014-11-01 00:00:00
abstract:BACKGROUND:While standards for the treatment of newly diagnosed glioblastomas exist, therapeutic regimens for tumor recurrence remain mostly individualized. The role of a surgical resection of recurrent glioblastomas remains largely unclear at present. This study aimed to assess the effect of repeated resection of recu...
journal_title:Neuro-oncology
pub_type: 杂志文章,多中心研究
doi:10.1093/neuonc/nov145
更新日期:2016-01-01 00:00:00
abstract:Background:Advances from glioma stemlike cell (GSC) research, though increasing our knowledge of glioblastoma (GBM) biology, do not influence clinical decisions yet. We explored the translational power of GSC-enriched cultures from patient-derived tumorspheres (TS) in predicting treatment response. Methods:The relatio...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/now304
更新日期:2017-08-01 00:00:00
abstract:Background:Malignant glioma (MG) is a devastating neuro-oncologic disease with almost invariably poor prognosis. Prognostic awareness (PA) is the awareness of incurable disease and shortened life expectancy (LE). Accurate PA is associated with favorable psychological outcomes at the end of life (EoL) for patients with ...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/nox117
更新日期:2017-10-19 00:00:00
abstract::Akt, one of the major downstream effectors of phosphatidylinositol 3-kinase, is hyper-expressed and activated in a variety of cancers including glioblastoma. However, the expression profiles of the Akt isoforms Akt1/PKBalpha, Akt2/PKBbeta, and Akt3/PKBgamma and their functional roles in malignant glioma are not well u...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/nop026
更新日期:2010-03-01 00:00:00
abstract:BACKGROUND:Anaplastic oligodendroglial tumors are rare, and median survival varies widely. Analysis of 1p19q deletion is performed commonly and is an important prognostic factor. However, age and other clinical variables also carry prognostic value, and it is unclear how to incorporate them into clinical decision makin...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/nou083
更新日期:2014-11-01 00:00:00
abstract::The objective of this study was to ascertain the duration of tumor control and the toxicities of dose-intense myeloablative chemotherapy for patients with recurrent oligodendrogliomas. Patients with previously irradiated oligodendrogliomas, either pure or mixed, that were contrast enhancing, measurable, and behaving a...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/2.2.114
更新日期:2000-04-01 00:00:00
abstract:BACKGROUND:This study aimed to evaluate the prognostic significance of co-polsomy of chromosome 1q and 19p in 1p/19q codeleted oligodendroglial tumors (ODGs). METHODS:In a series of 148 ODGs with 1p/19q deletion, co-polysomy of 1q and 19p was detected by fluorescence in situ hybridization (FISH). Log-rank analysis and...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/not092
更新日期:2013-09-01 00:00:00
abstract::The effects of combining histone deacetylase (HDAC) inhibitors and proteasome inhibitors were evaluated in both established glioblastoma multiforme (GBM) cell lines and short-term cultures derived from the Mayo Clinic xenograft GBM panel. Coexposure of LBH589 and bortezomib at minimally toxic doses of either drug alon...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1215/15228517-2007-063
更新日期:2008-06-01 00:00:00
abstract:BACKGROUND:Glioblastoma multiforme (GBM) is the most frequent malignant brain tumor in adults, and its prognosis remains dismal despite intensive research and therapeutic advances. Diagnostic biomarkers would be clinically meaningful to allow for early detection of the tumor and for those cases in which surgery is cont...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/not218
更新日期:2014-04-01 00:00:00
abstract::Diffuse low-grade glioma grows, migrates along white matter tracts, and progresses to high-grade glioma. Rather than a "wait and see" policy, an aggressive attitude is now recommended, with early surgery as the first therapy. Intraoperative mapping, with maximal resection according to functional boundaries, is associa...
journal_title:Neuro-oncology
pub_type: 杂志文章,评审
doi:10.1093/neuonc/nou153
更新日期:2015-03-01 00:00:00
abstract:BACKGROUND:Mutations involving isocitrate dehydrogenase 1 (IDH 1) occur in a high proportion of diffuse gliomas, with implications on diagnosis and prognosis. About 90% involve exon 4 at codon 132, replacing amino acid arginine with histidine (R132H). Rarer ones include R132C, R132S, R132G, R132L, R132V, and R132P. Mos...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/not015
更新日期:2013-06-01 00:00:00
abstract:Background:Children with brain tumors treated with cranial radiation therapy (RT) often exhibit cognitive late effects, commonly associated with reduced white matter (WM) volume and decreased neurogenesis. The impact of radiation damage in particular regions or tissues on brain development as a whole has not been eluci...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/nox211
更新日期:2018-05-18 00:00:00
abstract::Grade II gliomas are morphologically and clinically heterogeneous tumors for which histopathological typing remains the major tool for clinical classification. To what extent the major histological subtypes - astrocytomas, oligodendrogliomas, and oligoastrocytomas - constitute true biological entities is largely unres...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1215/15228517-2007-041
更新日期:2008-02-01 00:00:00
abstract::People with neurofibromatosis 1 (NF1) have multiple benign neurofibromas and a 10% lifetime risk of developing malignant peripheral nerve sheath tumors (MPNSTs). Most MPNSTs develop from benign plexiform neurofibromas, so the burden of benign tumors may be a risk factor for developing MPNST. We studied 13 NF1 patients...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1215/15228517-2008-011
更新日期:2008-08-01 00:00:00
abstract:Background:Previous reports have shown that overall incidence of malignant brain and other central nervous system (CNS) tumors varied significantly by country. The aim of this study was to estimate histology-specific incidence rates by global region and assess incidence variation by histology and age. Methods:Using da...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/nox091
更新日期:2017-10-19 00:00:00
abstract:BACKGROUND:The transcription factor homeobox C9 (HOXC9) plays a crucial role in developmental regulatory systems, where it determines the specific positional identities of cells along the anteroposterior axis. The expression of HOXC9 has been found to be dysregulated in some cancers such as lung cancer, breast cancer, ...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/nov281
更新日期:2016-06-01 00:00:00
abstract:BACKGROUND:Meningiomas are the most commonly diagnosed primary intracranial neoplasms. Despite significant advances in modern therapies, the management of malignant meningioma and skull base meningioma remains a challenge. Thus, the development of new treatment modalities is urgently needed for these difficult-to-treat...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/not007
更新日期:2013-06-01 00:00:00
abstract::A growing body of epidemiologic and tumor genomic research has identified an important role for telomere maintenance in glioma susceptibility, initiation, and prognosis. Telomere length has long been investigated in relation to cancer, but whether longer or shorter telomere length might be associated with glioma risk ...
journal_title:Neuro-oncology
pub_type: 杂志文章,评审
doi:10.1093/neuonc/nov082
更新日期:2015-11-01 00:00:00
abstract:Background:Targeted approaches for treating glioblastoma (GBM) attempted to date have consistently failed, highlighting the imperative for treatment strategies that operate on different mechanistic principles. Bioenergetics deprivation has emerged as an effective therapeutic approach for various tumors. We have previou...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/nox243
更新日期:2018-06-18 00:00:00
abstract::Epidermal growth factor receptor (EGFR) gene amplification and activating mutations are common findings in glioblastomas. EGFR is at the top of a downstream signaling cascade that regulates important characteristics of glioblastoma cells, including cellular proliferation, migration, and survival. Targeting EGFR has th...
journal_title:Neuro-oncology
pub_type: 杂志文章,评审
doi:10.1093/neuonc/nou222
更新日期:2014-10-01 00:00:00
abstract:BACKGROUND:We assessed the longitudinal hazard characteristics for death and progression in patients with glioblastoma, evaluated the impact of prognostic factors and treatment on the hazard within different time intervals to determine if effects are time varying, and quantified the influence of progression on survival...
journal_title:Neuro-oncology
pub_type: 杂志文章,随机对照试验
doi:10.1093/neuonc/nov009
更新日期:2015-07-01 00:00:00